Kollegin Germain Cornelissen (MLS) schreibt:“As we are reaching the end of the year, it is a time to reflect. There are so many things we can be thankful for. Thanks to our team in Minnesota and many colleagues worldwide, the HCC has been as active and as productive as ever. This year’s highlights are summarized below.The invitation to become a JAXA/NASA investigator led to a new project with Professor Kuniaki Otsuka on the ECG monitoring of astronauts during long-term missions on the International Space Station. Although endpoints of heart rate variability (HRV) followed a circadian rhythm in space as on earth, the fractal scaling of the long-term HRV experienced significant and consistent disruption under microgravity conditions, especially when the participants were awake. The results hold important implications for long-term space missions as they suggest that the intrinsic cardiovascular autonomic regulatory system may not adapt to microgravity in space. These results were published in npj Microgravity [1].

Also with Kuniaki, analyses of our database of 7-day/24-hour ABPM data collected in a community in northern Japan investigated the effect of mild depression on blood pressure. Results indicate that even a mildly depressive mood was associated with shorter sleep duration, lower subjective quality of life and happiness, and altered 7-day/24-hour systolic blood pressure variability [2], stressing the importance of monitoring blood pressure for longer 24 hours. These findings, together with several detailed case reports are part of a book on chronomics soon to become available from Springer [3].With Professor Jarmila Siegelova and her team, we examined the database of 7-day/24-hour ABPM data she collected at Masaryk University, Brno, Czech Republic to quantify the novelty pressor effect by comparing circadian rhythm parameters in consecutive days of monitoring. We found that on the first day, blood pressure was 2-3.5 mmHg higher and the circadian double amplitude of blood pressure 3-4 mmHg larger on average as compared to subsequent days. Moreover, we found that the novelty pressor effect on the circadian amplitude of blood pressure can last longer than 24 hours [4]. Further evidence underlying the need for 7-day/24-hour ABPM and for their chronobiologic interpretation was also presented at the yearly meeting on Noninvasive Methods in Cardiology organized by Jarmila [5].Within the scope of our project on the BIOsphere and the COSmos (BIOCOS), changes in blood pressure and heart rate during a 2-month stay at the Mendel research base in Antarctica were evaluated in a group of participants of the 5th and 6th Czech Antarctic Scientific Expeditions, by comparison to ABPM recordings in their home country. On the average, blood pressure and heart rate in Antarctica were significantly elevated and there was a higher prevalence of circadian overswing (or CHAT, Circadian Hyper-Amplitude-Tension, a condition associated with an increased cardiovascular disease risk even in the absence of high blood pressure) [6].Cooperation continued with Dr. Ram B Singh in the fields of cardiology and nutrition. As editors of the World Heart Journal, we seek to increase the impact of the journal as well as the awareness of chronobiologic principles as they relate to health surveillance and maintenance, diagnosis and prognosis, and treatment optimization by timing.Also within the scope of BIOCOS, in cooperation with Professors RK and Ranjana Singh, the circadian rhythm of circulating plasma lipid components was assessed in healthy Indians of different age groups. Total cholesterol, phospholipids and total lipids were found to be higher in females than in males, whereas the opposite held for HDL-cholesterol. Trends with age were not invariably linear: HDL-cholesterol, phospholipids, and total lipids were found to reach a maximum around mid-adulthood, as did the circadian amplitude of phospholipids, whereas the circadian amplitude of total cholesterol was minimal around mid-adulthood [7]. We also determined the circadian rhythm of lipid peroxides and anti-oxidant defense mechanisms in patients with peptic ulcers as compared to age-matched clinically healthy volunteers. Patients were found to have lower malondialdehyde, blood superoxide dismutase, glutathione peroxide, glutathione reductase, ascorbic acid, and HDL-cholesterol, as well as a dampened circadian variation of these variables, except for malondialdehyde and albumin that had an amplified circadian rhythm [8]. These results are presently being included in an invited chapter on cholesterol.Another ongoing BIOCOS project is underway in Siberia with Professor Denis Gubin. Several databases are being assembled of emergencies resulting in a call for an ambulance. The circadian pattern of the incidence of several disease conditions is being assessed and compared in different age groups and in several geographic locations differing greatly in their latitude.Cooperation continued with Professor Weihong Pan, now Medical Director of the Biopotentials Sleep Center in Baton Rouge, LA. With her, we studied how sleep fragmentation blunts the circadian variation of autophagy in mouse hippocampus. A manuscript is currently being considered for publication.With Elizabeth Lusczek, Assistant Professor in the department of surgery at the University of Minnesota, a pilot study is under way to monitor circadian rhythms of vital signs in healthy people and in patients admitted in the intensive care unit. This feasibility study will serve as a reference for assessing planned interventions to strengthen the circadian system of patients with the aim to improve outcomes such as length of hospital stay and the incidence of complications.At the HCC, Cathy Lee Gierke completed her project “Testing Chronomics Analysis Toolkit (CATkit)”, funded by the University of Minnesota Retiree Association. CATkit is an R package for analysis of periodicities in time series and open-source suite of rhythm analysis tools running on UNIX, Windows and Macintosh platforms. Cathy published [9] and presented her work at the Gordon Research Conference on Chronobiology held in Girona, Spain from June 28 to July 3, 2015. She was also invited to present applications of her software at the meeting in Brno [10] and at the first meeting of the newly founded Indian Society for Chronomedicine held in Ahmedabad, India on November 22-23, 2015, where Germaine was invited to deliver the keynote lecture. Professor Douglas Wilson, who also lectured in Ahmedabad, offered to do the beta-testing of Cathy’s software. Work at the HCC on blood pressure variability was also prominently featured at the 8th International Congress of Cardiovascular Diseases held on August 13-15 in Recife, Brazil.The HCC keeps attracting visitors. Continuing a long-term tradition, Professor Yoshihiko Watanabe came to work with us to optimize the administration of several anti-hypertensive drug combinations by timing. His 7-day/24-hour ABPM records of patients treated daily with losartan-hydrochlorothiazide at each of 6 different circadian stages during consecutive monthly spans have been further analyzed. Estimates of the circadian rhythm characteristics were obtained on a daily basis in order to assess the circadian-stage-dependent response to treatment on a personalized basis [11]. Results indicate that well over 50% of the patients are likely to benefit from the individual optimization of treatment timing (chronotherapy) by further lowering of blood pressure and/or by the elimination of other abnormal patterns of blood pressure and heart rate variability (the vascular variability disorders).Dr. Fabien De Meester also visited the HCC this year to discuss ways of improving the yield of chicken farms by manipulating environmental synchronizers. With Professor Noel Petit from Augsburg College and John Uldrich, results on “Nowcasting of human health hazards from terrestrial and space weather” were presented at an Expert Meeting on Biometeorological and Bioclimatic Forecasts held on November 30 – December 2 in Havana, Cuba. To warnings now issued by Med-Weather in relation to changes in weather conditions, merits of mapping long-term periodicities shared between space weather and biota were discussed at the conference. Emphasis was placed on ongoing plans at the HCC for an “atlas of chronomes” (broad time structures, defined by their rhythm characteristics: period, amplitude and phase) aiming to better understand broad environmental influences on human health. While these data were presented by Noel Petit in Cuba, Germaine delivered her invited lecture on a related topic at the 12th European Space Weather Week on November 26 in Oostende, Belgium. Based on multiple records of environmental and biological data, she pointed out that shared periodicities may trickle down from space to earth via the ionosphere, weather conditions, and economic cycles. Influences of space and terrestrial weather on human physiology and pathology were also the topic of an invited chapter in PJ Rosch’s book on Bioelectromagnetic and Subtle Energy Medicine [12].Thanks to staff at the HCC, Mary Sampson and Cathy Lee Gierke in particular, and with help from Professor Miguel Revilla and Nancy Rowe, we have a new website. Please visit us at http://halbergchronobiologycenter.umn.edu where you can meet our key collaborators, download some tutorials on chronobiology and see recently published titles. You will also find the full bibliography of Franz Halberg along with his curriculum vitae, interviews he gave, an autobiography, and a page illustrating his life in pictures. A recent article [13] summarizing the two main avenues of research that are the mandate of the HCC, namely clinical applications of the chronobiologic interpretation of around-the-clock blood pressure and heart rate records on the one hand and the study of environmental influences on human physiopathology on the other hand, is also available from our website.This year, the HCC was very happy to see several students from Integrative Biology and Physiology opting to learn about topics in chronobiology to write their term paper. James Fleming stayed on to work on a research project which he presented at Cardio Palooza 7 on July 29, 2015, a venue organized jointly between the department of Integrative Biology and Physiology and the Lillehei Institute (Cardiology) with which our HCC is affiliated. There, he showed how several aspects of the circadian rhythm in LF/HF, a frequency-domain endpoint of heart rate variability reflecting sympathetic activity, changes as a function of age.The HCC continues to benefit from cooperation with many more colleagues locally, nationally, and internationally. In particular, we are grateful to Drs. Francine and Julia Halberg who serve as advisors to the HCC. Their continued support of activities at the HCC is much appreciated.

With the Season’s Greetings from the Halberg Chronobiology Center and BIOCOS.

Hristova K, Singh RB, Cornelissen G, Fedacko J, Pella D, Chaves H, Elkilany G, Otsuka K, for the International College of Cardiology. The challenges of new guidelines for management of hypertension: a view point of the International College of Cardiology. World Heart J 2015; 7 (3): 103-107.